Combinatorial Laboratories

In the early 1990s, a new approach debuted, focusing on synthesis of collections of compounds or libraries rather than individual compounds. This development was viewed to have great promise for enhancing drug discovery. Initial work concentrated on production of extremely large libraries, up to several hundred thousand compounds, for screening to discover new lead compounds. These libraries were usually produced as combinatorial libraries: mixtures of compounds, split into pools, with no individual member being purified prior to use.

In the late 1990s, it was generally recognized that these libraries were actually particularly poor sources for lead discovery since the physical character of the compounds is quite similar and does not functionally give a wide diversity. This concept of functional diversity has now become one of the centerpieces industrially in the design and use of combinatorial libraries.

In academic circles, many chemistry departments seized upon the opportunity to develop new types of chemistries for the production libraries. Consequently, most academic research in the area has concentrated upon developing highly diverse, very large combinatorial libraries that are produced using new chemistries developed for that purpose.

By contrast at UCSF, scientists have continually concentrated their efforts on the development of libraries as tools for answering specific questions in medical research.

Therefore, the libraries produced at UCSF are smaller in scope, but much more clearly defined. Each compound is designed for a specific purpose, produced separately, and highly purified.

The Center for Chemical Diversity will provide a central location for production of chemically diverse yet targeted libraries and the development of techniques of parallel chemistry.

The production and acquisition of these libraries will be highly linked with underlying biological and clinical research at UCSF. The Center's combinatorial infrastructure will also serve as a nucleus for the use of libraries on campus: providing storage of libraries, enabling non-chemists to access all appropriate compounds through the center, and allowing researchers to design and make custom libraries for their studies.

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